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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Hyperthyroidism is a state in which the body is producing too much thyroid hormone. The main hyperthyroid conditions are:
- Graves' disease
- Toxic thyroid nodule
- Thyroid storm
- Toxic nodular struma (Plummer's disease)
- Hashitoxicosis: "transient" hyperthyroidism that can occur in Hashimoto's thyroiditis
Certain medications can have the unintended side effect of affecting thyroid function. While some medications can lead to significant hypothyroidism or hyperthyroidism and those at risk will need to be carefully monitored, some medications may affect thyroid hormone lab tests without causing any symptoms or clinical changes, and may not require treatment. The following medications have been linked to various forms of thyroid disease:
- Amiodarone (more commonly can lead to hypothyroidism, but can be associated with some types of hyperthyroidism)
- Lithium salts (hypothyroidism)
- Some types of interferon and IL-2 (thyroiditis)
- Glucocorticoids, dopamine agonists, and somatostatin analogs (block TSH, which can lead to hypothyroidism)
Women being treated for Hashimoto's disease can become pregnant. It is recommended that thyroid function be well-controlled before getting pregnant.
Untreated or poorly treated underactive thyroid can lead to problems for the mother, such as:
- Preeclampsia
- Anemia
- Miscarriage
- Placental abruption
- High cholesterol
- Postpartum bleeding
It also can cause serious problems for the baby, such as:
- Preterm birth
- Low birth weight
- Stillbirth
- Birth defects
- Thyroid problems
Sequence of events:
1. Iodine deficiency leading to decreased T4 production.
2. Induction of thyroid cell hyperplasia due to low levels of T4. This accounts for the multinodular goitre appearance.
3. Increased replication predisposes to a risk of mutation in the TSH receptor.
4. If the mutated TSH receptor is constitutively active, it would then become 'toxic' and produces excess T3/T4 leading to hyperthyroidism.
Thyroid nodules are nodules (raised areas of tissue or fluid) which commonly arise within an otherwise normal thyroid gland. They may be hyperplasia or a thyroid neoplasm, but only a small percentage of the latter are thyroid cancers. Small, asymptomatic nodules are common, and many people who have them are unaware of them. But nodules that grow larger or produce symptoms may eventually need medical care. Goitres may have nodules or be diffuse.
Normal hormone changes during pregnancy cause thyroid hormone levels to increase. The thyroid may enlarge slightly in healthy women during pregnancy, but not enough to be felt. These changes do not affect the pregnancy or unborn baby. Yet, untreated thyroid problems can threaten pregnancy and the growing baby. Symptoms of normal pregnancy, like fatigue, can make it easy to overlook thyroid problems in pregnancy.
Thyroid hormone is vital during pregnancy. The unborn baby's brain and nervous system need thyroid hormone to develop. During the first trimester, the baby depends on the mother's supply of thyroid hormone. At 10 to 12 weeks of pregnancy, the baby's thyroid begins to work on its own. But the baby still depends on the mother for iodine, which the thyroid uses to make thyroid hormone. Pregnant women need about 250 micrograms (mcg) of iodine a day. Some women might not get all the iodine they need through the foods they eat or prenatal vitamins. Using iodized salt — salt that has had iodine added to it over plain table salt is recommended. Prenatal vitamins that contain iodine are also recommended.
Some women develop thyroid problems in the first year after giving birth. This is called postpartum thyroiditis. It often begins with symptoms of an overactive thyroid, which last 2 to 4 months. Mild symptoms might be overlooked. Affected women then develop symptoms of an underactive thyroid, which can last up to a year. An underactive thyroid needs to be treated. In most cases, thyroid function returns to normal as the thyroid heals.
Surgery (thyroidectomy) may be indicated in the following instances:
- Reaccumulation of the nodule despite 3–4 repeated FNACs
- Size in excess of 4 cm in some cases
- Compressive symptoms
- Signs of malignancy (vocal cord dysfunction, lymphadenopathy)
- Cytopathology that does not exclude thyroid cancer
Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births. More than 1000 individuals have been identified with thyroid hormone resistance, of which 85% had thyroid hormone beta receptor mutation.
Parathyroid adenoma can be associated with overexpression of the cyclin D1 gene.
Thyroid dysgenesis or thyroid agenesis is a cause of congenital hypothyroidism where the thyroid is missing, ectopic, or severely underdeveloped.
It should not be confused with iodine deficiency, or with other forms of congenital hypothyroidism, such as thyroid dyshormonogenesis, where the thyroid is present but not functioning correctly.
Congenital hypothyroidism caused by thyroid dysgenesis can be associated with PAX8.
A parathyroid adenoma is a benign tumor of the parathyroid gland. It generally causes hyperparathyroidism; there are very few reports of parathyroid adenomas that were not associated with hyperparathyroidism.
A human being usually has four parathyroid glands located on the back surface of the thyroid in the neck. The parathyroids secrete parathyroid hormone (PTH), which increases the concentration of calcium in the blood by inducing the bones to release calcium into the blood and the kidneys to reabsorb it from the urine into the blood. When a parathyroid adenoma causes hyperparathyroidism, more parathyroid hormone is secreted, causing the calcium concentration of the blood to rise, resulting in hypercalcemia.
An "ectopic thyroid", also called "accessory thyroid gland", is a form of thyroid dysgenesis in which an entire or parts of the thyroid located in another part of the body than what is the usual case. A completely ectopic thyroid gland may be located anywhere along the path of the descent of the thyroid during its embryological development, although it is most commonly located at the base of the tongue, just posterior to the foramen cecum of the tongue. In this location, an aberrant or ectopic thyroid gland is known as a "lingual thyroid". If the thyroid fails to descend to even higher degree, then the resulting final resting point of the thyroid gland may be high in the neck, such as just below the hyoid bone. Parts of ectopic thyroid tissue ("accessory thyroid tissue") can also occur, and arises from remnants of the thyroglossal duct, and may appear anywhere along its original length. Accessory thyroid tissue may be functional, but is generally insufficient for normal function if the main thyroid gland is entirely removed.
Lingual thyroid is 4-7 times more common in females, with symptoms developing during puberty, pregnancy or menopause. Lingual thyroid may be asymptomatic, or give symptoms such as dysphagia (difficulty swallowing), dysphonia (difficulty talking) and dyspnea (difficulty breathing).
There are several causes of hyperthyroidism. Most often, the entire gland is overproducing thyroid hormone. Less commonly, a single nodule is responsible for the excess hormone secretion, called a "hot" nodule. Thyroiditis (inflammation of the thyroid) can also cause hyperthyroidism. Functional thyroid tissue producing an excess of thyroid hormone occurs in a number of clinical conditions.
The major causes in humans are:
- Graves' disease. An autoimmune disease (usually, the most common etiology with 50-80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981)). Thought to be due to varying levels of iodine in the diet. It is eight times more common in females than males and often occurs in young females, around 20 – 40 years of age.
- Toxic thyroid adenoma (the most common etiology in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country)
- Toxic multinodular goiter
High blood levels of thyroid hormones (most accurately termed hyperthyroxinemia) can occur for a number of other reasons:
- Inflammation of the thyroid is called thyroiditis. There are several different kinds of thyroiditis including Hashimoto's thyroiditis (Hypothyroidism immune-mediated), and subacute thyroiditis (de Quervain's). These may be "initially" associated with secretion of excess thyroid hormone but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism.
- Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of consumption of ground beef contaminated with thyroid tissue, and thus thyroid hormone (termed "hamburger hyperthyroidism").
- Amiodarone, an antiarrhythmic drug, is structurally similar to thyroxine and may cause either under- or overactivity of the thyroid.
- Postpartum thyroiditis (PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment.
- A struma ovarii is a rare form of monodermal teratoma that contains mostly thyroid tissue, which leads to hyperthyroidism.
- Excess iodine consumption notably from algae such as kelp.
Thyrotoxicosis can also occur after taking too much thyroid hormone in the form of supplements, such as levothyroxine (a phenomenon known as exogenous thyrotoxicosis, alimentary thyrotoxicosis, or occult factitial thyrotoxicosis).
Hypersecretion of thyroid stimulating hormone (TSH), which in turn is almost always caused by a pituitary adenoma, accounts for much less than 1 percent of hyperthyroidism cases.
Hyperthyroidism is very rare in dogs, occurring in less than 1% of dogs. Hyperthyroidism may be caused by a thyroid tumor. This may be a thyroid carcinoma. About 90% of carcinomas are a very aggressive; they invade the surrounding tissues and metastasize (spread), to other tissues, particularly the lungs. This has a poor prognosis. Surgery to remove the tumor a carcinoma is often very difficult, due to the spread of the tumor to the surrounding tissue, for example, into arteries, the esophagus, or the windpipe. It may be possible to reduce the size of the tumor, thus relieving symptoms and allowing time for other treatments to work. About 10% of thyroid tumors are benign; these often cause few symptoms.
In dogs treated for hypothyroidism (lack of thyroid hormone), hyperthyroidism may occur as a result of an overdose of the thyroid hormone replacement medication, levothyroxine; in this case treatment involves reducing the dose of levothyroxine. Dogs which display coprophagy, that is, which often eat feces, and which live in a household with a dog receiving levothyroxine treatment, may develop hyperthryoidism if they frequently eat the feces from the dog receiving levothyroxine treatment.
Hyperthyroidism may occur if a dog eats an excessive amount of thyroid gland tissue. This has occurred in dogs fed commercial dog food.
Worldwide, the most common cause for goitre is iodine deficiency, usually seen in countries that do not use iodized salt. Selenium deficiency is also considered a contributing factor. In countries that use iodized salt, Hashimoto's thyroiditis is the most common cause. Goitre can also result from cyanide poisoning; this is particularly common in tropical countries where people eat the cyanide-rich cassava root as the staple food.
- Sarcoidosis
- Amyloidosis
- Hydatidiform mole
- Cysts
- Acromegaly
- Pendred syndrome
Worldwide about one billion people are estimated to be iodine deficient; however, it is unknown how often this results in hypothyroidism. In large population-based studies in Western countries with sufficient dietary iodine, 0.3–0.4% of the population have overt hypothyroidism. A larger proportion, 4.3–8.5%, have subclinical hypothyroidism. Of people with subclinical hypothyroidism, 80% have a TSH level below the 10 mIU/l mark regarded as the threshold for treatment. Children with subclinical hypothyroidism often return to normal thyroid function, and a small proportion develops overt hypothyroidism (as predicted by evolving antibody and TSH levels, the presence of celiac disease, and the presence of a goiter).
Women are more likely to develop hypothyroidism than men. In population-based studies, women were seven times more likely than men to have TSH levels above 10 mU/l. 2–4% of people with subclinical hypothyroidism will progress to overt hypothyroidism each year. The risk is higher in those with antibodies against thyroid peroxidase. Subclinical hypothyroidism is estimated to affect approximately 2% of children; in adults, subclinical hypothyroidism is more common in the elderly, and in Caucasians. There is a much higher rate of thyroid disorders, the most common of which is hypothyroidism, in individuals with Down syndrome and Turner syndrome.
Very severe hypothyroidism and myxedema coma are rare, with it estimated to occur in 0.22 per million people a year. The majority of cases occur in women over 60 years of age, although it may happen in all age groups.
Most hypothyroidism is primary in nature. Central/secondary hypothyroidism affects 1:20,000 to 1:80,000 of the population, or about one out of every thousand people with hypothyroidism.
Goitre is more common among women, but this includes the many types of goitre caused by autoimmune problems, and not only those caused by simple lack of iodine.
Depending on source, the overall 5-year survival rate for medullary thyroid cancer is 80%, 83% or 86%, and the 10-year survival rate is 75%.
By overall cancer staging into stages I to IV, the 5-year survival rate is 100% at stage I, 98% at stage II, 81% at stage III and 28% at stage IV. The prognosis of MTC is poorer than that of follicular and papillary thyroid cancer when it has metastasized (spread) beyond the thyroid gland.
The prognostic value of measuring calcitonin and carcinoembryonic antigen (CEA) concentrations in the blood was studied in 65 MTC patients who had abnormal calcitonin levels after surgery (total thyroidectomy and lymph node dissection). The prognosis correlated with the rate at which the postoperative calcitonin concentration doubles, termed the calcitonin doubling time (CDT), rather than the pre- or postoperative absolute calcitonin level:
- CDT less than 6 months: 3 patients out of 12 (25%) survived 5 years. 1 patient out of 12 (8%) survived 10 years. All died within 6 months to 13.3 years.
- CDT between 6 months and 2 years: 11 patients out of 12 (92%) survived 5 years. 3 patients out of 8 (37%) survived 10 years. 4 patients out of 12 (25%) survived to the end of the study.
- CDT more than 2 years: 41 patients out of 41 (100%) were alive at the end of the study. These included 1 patient whose calcitonin was stable, and 11 patients who had decreasing calcitonin levels.
The calcitonin doubling time was a better predictor of MTC survival than CEA but following both tests is recommended.
A pituitary disease is a disorder primarily affecting the pituitary gland.
The main disorders involving the pituitary gland are:
Overproduction or underproduction of a pituitary hormone will affect the respective end-organ. For example, insufficient production (hyposecretion) of thyroid stimulating hormone (TSH) in the pituitary gland will cause hypothyroidism, while overproduction (hypersecretion) of TSH will cause hyperthyroidism. Thyroidisms caused by the pituitary gland are less common though, accounting for less than 10% of all hypothyroidism cases and much less than 1% of hyperthyroidism cases.
Thyroid cancers are thought to be related to a number of environmental and genetic predisposing factors, but significant uncertainty remains regarding their causes.
Environmental exposure to ionizing radiation from both natural background sources and artificial sources is suspected to play a significant role, and there are significant increased rates of thyroid cancer in those exposed to mantlefield radiation for lymphoma, and those exposed to iodine-131 following the Chernobyl, Fukushima, Kyshtym, and Windscale nuclear disasters. Thyroiditis and other thyroid diseases also predispose to thyroid cancer.
Genetic causes include multiple endocrine neoplasia type 2 which markedly increases rates, particularly of the rarer medullary form of the disease.
Pregnant women who are positive for Hashimoto's thyroiditis may have decreased thyroid function or the gland may fail entirely. If a woman is TPOAb-positive, clinicians can inform her of the risks for themselves and their infants if they go untreated. "Thyroid peroxidase antibodies (TPOAb) are detected in 10% of pregnant women," which presents risks to those pregnancies. Women who have low thyroid function that has not been stabilized are at greater risk of having an infant with: low birth weight, neonatal respiratory distress, hydrocephalus, hypospadias, miscarriage, and preterm delivery. The embryo transplantion rate and successful pregnancy outcomes are improved when Hashimoto's is treated. Recommendations are to only treat pregnant women who are TPOAb-positive throughout the entirety of their pregnancies and to screen all pregnant women for thyroid levels. Close cooperation between the endocrinologist and obstetrician benefits the woman and the infant. The Endocrine Society recommends screening in pregnant women who are considered high-risk for thyroid autoimmune disease.
Thyroid peroxides antibodies testing is recommended for women who have ever been pregnant regardless of pregnancy outcome. "...[P]revious pregnancy plays a major role in development of autoimmune overt hypothyroidism in premenopausal women, and the number of previous pregnancies should be taken into account when evaluating the risk of hypothyroidism in a young women ["sic"]."
Toxic multinodular goiter (also known as toxic nodular goiter, or Plummer's disease) is a multinodular goiter associated with hyperthyroidism.
It is a common cause of hyperthyroidism in which there is excess production of thyroid hormones from functionally autonomous thyroid nodules, which do not require stimulation from thyroid stimulating hormone (TSH).
Toxic multinodular goiter is the second most common cause of hyperthyroidism (after Graves' disease) in the developed world, whereas iodine deficiency is the most common cause of hypothyroidism in developing-world countries where the population is iodine-deficient. (Decreased iodine leads to decreased thyroid hormone.) However, iodine deficiency can cause goitre (thyroid enlargement); within a goitre, nodules can develop. Risk factors for toxic multinodular goiter include individuals over 60 years of age and being female.
Almost all thyroid adenomas are follicular adenomas. Follicular adenomas can be described as "cold", "warm" or "hot" depending on their level of function. Histopathologically, follicular adenomas can be classified according to their cellular architecture and relative amounts of cellularity and colloid into the following types:
- Fetal (microfollicular) - these have the potential for microinvasion. These consist of small, closely packed follicles lined with epithelium.
- colloid (macrofollicular) - these do "not" have any potential for microinvasion
- embryonal (atypical) - have the potential for microinvasion.
- Hürthle cell adenoma (oxyphil or oncocytic tumor) - have the potential for microinvasion.
- Hyalinizing trabecular adenoma
Papillary adenomas are very rare.
A cold nodule is a thyroid nodule that does not produce thyroid hormone. On a radioactive iodine uptake test a cold nodule takes up less radioactive material than the surrounding thyroid tissue. A cold nodule may be malignant or benign. On scintigraphy cold nodules do not show but are easily shown on ultrasound. Figure 1 illustrates the basic anatomy of the thyroid gland. The case shown in Figure 4 shows a cold nodule quite emphasized representation of the thyroid. The investigation was carried out due to a goiter rating of 3. Striking was the discrepancy between the magnification sonographically depicted the thyroid lobe and the findings in the scintigraphy; the lower part of the right lobe and the lateral part of the left missing in the bone scan, although demonstrably thyroid tissue is present there sonographically. This imperfective representation for thyroid tissue is the characteristic of "cold node".
Neonatal thyroid screening programs from all over the world have revealed that congenital hypothyroidism (CH) occurs with an incidence of 1:3000 to 1:4000. The differences in CH-incidence are more likely due to iodine deficiency thyroid disorders or to the type of screening method than to ethnic affiliation. CH is caused by an absent or defective thyroid gland classified into agenesis (22-42%), ectopy (35-42%) and gland in place defects (24-36%). It is also found to be of increased association with female sex and gestational age >40 weeks.